The mode of action of opiates in analgesia, tolerance and physical dependence is being assessed by studying their interactions with Ca ions and B-endorphin. Continuing studies will involve: (1) Effect of morphine acutely and chronically on Ca ions uptake in subcellular components of lysed synaptosomes. (2) Effect of morphine on Ca ions uptake induced by K ion depolarization. (3) Ca ions antagonism of morphine effects on the isolated guinea pig ileum. (4) Similar studies with B-endorphin.